scholarly journals Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Zhou ◽  
Yuan Li ◽  
Lujun Chen ◽  
Xiao Zheng ◽  
Tianwei Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Target Genes ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Regulatory Relationship ◽  
Downstream Target

Long non-coding RNAs (lncRNAs) play important roles in various biological processes and human diseases, including cancer. In this study, we demonstrated a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration, and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target genes of miR-375, and established the important role of the GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Taken together, our results revealed a novel mechanism of GRIK1-AS1 as a sponge to miR-375 that impacts gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, opens a new strategy to future GRIK1-AS1 based therapeutic development.

scholarly journals Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 axis

2020 ◽  
Author(s):  
Qi Zhou ◽  
Yuan Li ◽  
Lujun Chen ◽  
Xiao Zheng ◽  
Tianwei Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Regulatory Relationship ◽  
Downstream Target ◽  
Rnai Technology

Abstract Backgroud Long non-coding RNAs (lncRNAs) played important roles in various biological processes and human diseases, including cancer. Methods In this study, RNAi technology, RNA-FISH, RNA-pull down assay and cellular function studies were used to demonstrate a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Results Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target gene of miR-375, and established the important role of GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Conclusions Our results revealed a novel mechanism of GRIK1-AS1 as sponge to miR-375that impact gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, open a new strategy to future GRIK1-AS1 based therapeutic development.

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

scholarly journals Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1820
Author(s):  
Chengcheng Hao ◽  
Yuxin Cui ◽  
Jane Lane ◽  
Shuqin Jia ◽  
Jiafu Ji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Prognostic Value ◽  
Splice Variants ◽  
Tnm Staging ◽  
Migration And Invasion ◽  
Ros Production ◽  
Gastric Cancer Cells ◽  
Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

scholarly journals CDX2 and Reg IV expression and correlation in gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dandan Chai ◽  
Huifen Du ◽  
Kesheng Li ◽  
Xueliang Zhang ◽  
Xiaoqin Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Real Time ◽  
Real Time Pcr ◽  
Ectopic Expression ◽  
Rank Correlation ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion

Abstract Background Ectopic expression of CDX2 is associated with the development and progression of gastric cancer. Previous studies showed that CDX2 may be an upstream regulator of Reg IV expression in gastric cancer, and our previous report showed that Reg IV upregulated SOX9 expression and enhanced cell migration and invasion in gastric cancer cells. However, the regulatory roles of CDX2 have not been clarified in gastric cancer, and the correlation between CDX2 and Reg IV requires further study. Methods CDX2 and Reg IV were examined in gastric cancer specimens and paired adjacent tissues via real-time PCR and immunohistochemistry (IHC). The association between CDX2 and Reg IV was assessed using the χ2-test and Spearman’s rank correlation. To verify their relationship, knockdown and exogenous expression of CDX2 or Reg IV were performed in AGS and MKN-45 gastric cancer cells, and their expression was subsequently analyzed via a real-time PCR and western blotting. Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression. Results A positive correlation was observed between CDX2 and Reg IV expression at the mRNA and protein levels in gastric cancer tissues. CDX2 silencing significantly downregulated Reg IV expression, and CDX2 overexpression significantly upregulated Reg IV expression in AGS and MKN-45 cells. Neither Reg IV silencing nor overexpression had any effect on CDX2 protein expression in AGS or MKN-45 cells, even though both affected the expression of CDX2 mRNA. Functionally, CDX2 silencing significantly inhibited cell migration and invasion, and CDX2 overexpression significantly promoted cell migration and invasion in AGS and MKN-45 cells. Conclusions Our findings demonstrate that CDX2 expression was positively correlated with that of Reg IV in gastric cancer, and CDX2 promoted cell migration and invasion through upregulation of Reg IV expression in AGS and MKN-45 cells.

scholarly journals Sevoflurane represses the migration and invasion of gastric cancer cells by regulating forkhead box protein 3

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Fangfang Yong ◽  
Hemei Wang ◽  
Chao Li ◽  
Huiqun Jia
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cell Lines ◽  
Migration And Invasion ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Forkhead Box ◽  
Induced Apoptosis

Objective Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells. Methods GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively. Results FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells. Conclusions Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.

scholarly journals MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

2009 ◽  
Vol 20 (24) ◽  
pp. 5127-5137 ◽  
Author(s):  
Kai-Wen Hsu ◽  
Rong-Hong Hsieh ◽  
Chew-Wun Wu ◽  
Chin-Wen Chi ◽  
Yan-Hwa Wu Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Suppressive Effect ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Cox 2

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

scholarly journals NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

2020 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Yan He ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Hippo Pathway ◽  
Critical Role ◽  
Xenograft Model ◽  
Migration And Invasion

Abstract Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

scholarly journals miR-335-5p Suppresses Gastric Cancer Progression by Targeting MAPK10

2020 ◽  
Author(s):  
Yi Gao ◽  
Yanfeng Wang ◽  
Xiaofei Wang ◽  
Changan Zhao ◽  
Fenghui Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Target Gene ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Aberrant Expression ◽  
Related Target

Abstract Background: In recent years, many microRNAs(miRNAs) involved in cancer progression. The aberrant expression of miR-335-5p in tumorigenesis has been demonstrated. The present study aimed to investigate the molecular mechanisms underlying miR-335-5p- regulated MAPK10 expression in human gastric cancer（GC）.Methods: The quantitative real-time PCR was used to study the level of miR-335-5p expression in gastric cancer cell lines and tissues. Subsequently, the MTT and cloning formation assays were used to detect cell proliferation, while transwell and wound-healing assays were used to identify invasion and migration of the gastric cancer cells. The correlation between the miR-335-5p and the cell cycle-related target gene mitogen‑activated protein kinase 10 (MAPK10) in gastric cancer was analyzed based on the website. In addition, the target gene of miR-335-5p was detected by luciferase reporter assay, qRT-PCR, and western blotting.Results: The miR-335-5p level was down-regulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited proliferation, migration of gastric cancer cells, and induced apoptosis. During the G1/S phase, miR-335-5p arrested the cycle of gastric cancer cells in vitro. The correlation between the miR-335-5p and the cell cycle-related target gene MAPK10 in GC was analyzed, MAPK10 was directly targeted by the miR-335-5p.Conclusion: These data suggested that miR-335-5p acts as a tumor suppressor, and go through the MAPK10 to inhibit the GC progression.

scholarly journals CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ling Gao ◽  
Tingting Xia ◽  
Mingde Qin ◽  
Xiaofeng Xue ◽  
Linhua Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
High Morbidity ◽  
Gastric Cancer Cells ◽  
Mirna Sponges ◽  
Gastric Cancer Cell Proliferation

BackgroundGastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.MethodsCircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK).ResultsThe level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer.ConclusionCollectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.

scholarly journals PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingmin Sun ◽  
Mengyun Yuan ◽  
Hongxing Wang ◽  
Xingxing Zhang ◽  
Ruijuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Nuclear Translocation ◽  
Aerobic Glycolysis ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

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